That sleep is important for health is indicated by recent studies from this laboratory. Rats subjected to chronic total sleep deprivation or paradoxical (REM) sleep deprivation showed debilitated appearance, skin lesions on the paws and tail, decreased body temperature, increased energy expenditure, decreased serum thyroxine, increased serum norepinephrine, and eventual death. The research proposed below is oriented toward clarifying and elaborating upon these results. 1. To evaluate whether impaired heat retention is the "core" pathology in sleep deprived rats, we will determine whether sleep deprived rats self-select warm temperatures. Also we will determine whether deprivation-induced pathology is exacerbated in a cold ambient environment. 2. To evaluate whether the core pathology is mediated by sympathetic activation, we will determine whether the effects of sleep deprivation are blunted by maintaining rats on guanethidine, which blocks transmission at postganglionic sympathetic terminals. 3. To evaluate whether the core pathology is an increased metabolic rate, we will determine whether deprivation-induced pathology is blunted by a prior thyroidectomy. 4. We propose to complete studies on the reversibility of pathology induced by sleep deprivation. 5. To evaluate whether the increase in energy expenditure is mediated by the presence of an unidentified blood borne substance, we will circulate the blood of a deprived rat through a recipient rat while the metabolic rate of the recipient rat's intestine is monitored on-line 6. We proposed to evaluate the effects of sleep deprivation on immune function, mitosis, and cell structure.